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CD138 multiple myeloma

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https://www.readbyqxmd.com/read/29773987/celastrol-attenuates-the-invasion-and-migration-and-augments-the-anticancer-effects-of-bortezomib-in-a-xenograft-mouse-model-of-multiple-myeloma
#1
Muthu K Shanmugam, Kwang S Ahn, Jong H Lee, Radhamani Kannaiyan, Nurulhuda Mustafa, Kanjoormana A Manu, Kodappully S Siveen, Gautam Sethi, Wee J Chng, Alan P Kumar
Several lines of evidence have demonstrated that deregulated activation of NF-κB plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-κB upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated. In addition, we studied whether CSL can potentiate the apoptotic effect of bortezomib, a proteasome inhibitor in MM cells and in a xenograft mouse model...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29761903/the-combination-of-a-sphingosine-kinase-2-inhibitor-abc294640-and-a-bcl-2-inhibitor-abt-199-displays-synergistic-anti-myeloma-effects-in-myeloma-cells-without-a-t-11-14-translocation
#2
Pasupathi Sundaramoorthy, Cristina Gasparetto, Yubin Kang
Multiple myeloma (MM) remains an incurable disease in need of the development of novel therapeutic agents and drug combinations. ABT-199 is a specific Bcl-2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co-expression of Mcl-1 and Bcl-xL. These limitations preclude its use in a broader patient population. We have recently found that a sphingosine kinase 2-specific inhibitor (ABC294640) induces apoptosis in primary human CD138+ cells and MM cell lines...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29695719/the-multiple-myeloma-risk-allele-at-5q15-lowers-ell2-expression-and-increases-ribosomal-gene-expression
#3
Mina Ali, Ram Ajore, Anna-Karin Wihlborg, Abhishek Niroula, Bhairavi Swaminathan, Ellinor Johnsson, Owen W Stephens, Gareth Morgan, Tobias Meissner, Ingemar Turesson, Hartmut Goldschmidt, Ulf-Henrik Mellqvist, Urban Gullberg, Markus Hansson, Kari Hemminki, Hareth Nahi, Anders Waage, Niels Weinhold, Björn Nilsson
Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined  = 2.5 × 10-27 ; βcombined  = -0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines...
April 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29690814/concurrent-progressive-multifocal-leukoencephalopathy-and-central-nervous-system-infiltration-by-multiple-myeloma-a-case-report
#4
Yanira Ruiz-Heredia, Beatriz Sanchez-Vega, Santiago Barrio, María Linares, Inmaculada Rapado, Esteban Braggio, Keith Stewart, M Dolores Folgueira, Ana Ramos, Luis Collado, Juan Ruiz, Oscar Toldos, Aurelio Hernandez-Lain, Joaquin Martinez-Lopez
Progressive multifocal leukoencephalopathy rarely occurs in patients with multiple myeloma. Intracranial central nervous system invasion is also an uncommon event in multiple myeloma, occurring in less than 1% of cases. We describe herein an exceptional case of coexisting progressive multifocal leukoencephalopathy and intraparenchymal central nervous system myeloma infiltration. A 73-year-old woman with relapsed multiple myeloma was treated with 15 cycles of lenalidomide and dexamethasone, but therapy had to be stopped because of a hip fracture after a fall...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29666962/activity-of-indatuximab-ravtansine-against-triple-negative-breast-cancer-in-preclinical-tumor-models
#5
Kurt Schönfeld, Peter Herbener, Chantal Zuber, Thomas Häder, Katrin Bernöster, Christoph Uherek, Jörg Schüttrumpf
PURPOSE: Triple-negative breast cancer (TNBC) is related with a poor prognosis as patients do hardly benefit from approved therapies. CD138 (Syndecan-1) is upregulated on human breast cancers. Indatuximab ravtansine (BT062) is an antibody-drug-conjugate that specifically targets CD138-expressing cells and has previously shown clinical activity in multiple myeloma. Here we show indatuximab ravtansine as a potential mono- and combination therapy for TNBC. METHODS: The effects of indatuximab ravtansine were assessed in vitro in SK-BR-3 and T47D breast cancer cell lines...
April 17, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29652626/endosteal-and-perivascular-subniches-in-a-3d-bone-marrow-model-for-multiple-myeloma
#6
Maaike Vera Jasmijn Braham, Tilman Ahlfeld, Ashwini Rahul Akkineni, Monique C Minnema, Wouter Dhert, F Cumhur Oner, Catherine Robin, Anja Lode, Michael Gelinsky, Jacqueline Alblas
The bone marrow microenvironment is the preferred location of multiple myeloma, supporting tumor growth and development. It is composed of a collection of interacting subniches, including the endosteal and perivascular niche. Current in vitro models mimic either of these subniches. By developing a model combining both niches, this study aims to further enhance the ability to culture primary myeloma cells in vitro. Also the dependency of myeloma cells on each niche was studied. A 3D bone marrow model containing two subniches was created using 3D bioprinting technology...
March 8, 2018: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/29616859/expression-of-functional-folate-receptors-in-multiple-myeloma
#7
Ying Zhou, Kenji Unno, Elizabeth Hyjek, Hui Liu, Todd Zimmerman, Subhradip Karmakar, Karson S Putt, Jiayin Shen, Philip S Low, Amittha Wickrema
Receptor-targeted delivery of imaging and therapeutic agents has emerged as an attractive strategy to diagnosis and treat many diseases including cancer. One of the most well-studied receptors for targeted therapies is the folate receptor (FR) family. FR-α and FR-β are present on many cancers with little expression in normal tissues; leading to the testing of at least six folate-targeted drugs in human clinical trials for various cancers. However, the expression of FR in blood cancers has not been fully explored with no reports of FR expression in myelomas...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29545347/a-novel-nano-immunoassay-method-for-quantification-of-proteins-from-cd138-purified-myeloma-cells-biological-and-clinical-utility
#8
Irena Misiewicz-Krzeminska, Luis Antonio Corchete, Elizabeta A Rojas, Joaquín Martínez-López, Ramón García-Sanz, Albert Oriol, Joan Bladé, Juan-José Lahuerta, Jesús San Miguel, María-Victoria Mateos, Norma C Gutiérrez
Protein analysis in bone marrow samples from patients with multiple myeloma has been limited by the low concentration of proteins obtained after CD138+ cell selection. A novel approach based on capillary nano-immunoassay could make it possible to quantify dozens of proteins from each myeloma sample in an automated manner. Here we present a method for the accurate and robust quantification of the expression of multiple proteins extracted from CD138-purified multiple myeloma samples frozen in RLT Plus buffer, which is commonly used for nucleic acid preservation and isolation...
May 2018: Haematologica
https://www.readbyqxmd.com/read/29507674/comparison-of-immuno-pet-of-cd138-and-pet-imaging-with-64-cucl-2-and-18-f-fdg-in-a-preclinical-syngeneic-model-of-multiple-myeloma
#9
Clément Bailly, Sébastien Gouard, Marie Lacombe, Patricia Remaud-Le Saëc, Benjamin Chalopin, Mickaël Bourgeois, Nicolas Chouin, Raphaël Tripier, Zakaria Halime, Ferid Haddad, Alain Faivre-Chauvet, Françoise Kraeber-Bodéré, Michel Chérel, Caroline Bodet-Milin
Purpose: Although recent data from the literature suggest that PET imaging with [18]-Fluorodeoxyglucose (18 F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated a 64 Cu-labeled anti-CD138 murine antibody (64 Cu-TE2A-9E7.4) and a metabolic tracer (64 CuCl2 ) for PET imaging in a MM syngeneic mouse model...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29487385/histone-deacetylase-hdac-inhibitor-acy241-enhances-anti-tumor-activities-of-antigen-specific-central-memory-cytotoxic-t-lymphocytes-against-multiple-myeloma-and-solid-tumors
#10
Jooeun Bae, Teru Hideshima, Yu-Tzu Tai, Yan Song, Paul Richardson, Noopur Raje, Nikhil C Munshi, Kenneth C Anderson
Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138+ MM cells, CD4+ CD25+ FoxP3+ regulatory T cells, and HLA-DRLow/- CD11b+ CD33+ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+ T cells and of immune checkpoints in bone marrow cells from myeloma patients...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29454645/characterization-of-cd4-t-cell-mediated-cytotoxicity-in-patients-with-multiple-myeloma
#11
Xiaole Zhang, Lei Gao, Kai Meng, Chunting Han, Qiang Li, Zhenjun Feng, Lei Chen
Multiple myeloma (MM) is an incurable cancer characterized by the development of malignant plasma cells. The CD8 T cell-mediated cytotoxicity is considered a major player in antitumor immunity, but in MM patients, the CD8 T cells displayed senescence markers and were functionally impaired. To investigate whether cytotoxic CD4 T cells could act as a treatment alternative in MM, we examined the frequency and function of naturally occurring cytotoxic CD4 T cells in MM patients. The cytotoxic CD4 T cells were identified as granzyme-A, granzyme B-, and perforin-expressing CD4 T cells, and their frequencies were significantly upregulated in MM patients when compared with healthy controls...
May 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29421983/emerging-immune-targets-for-the-treatment-of-multiple-myeloma
#12
Atif Sohail, Adeela Mushtaq, Ahmad Iftikhar, Zabih Warraich, Sandra E Kurtin, Pavan Tenneti, Ali McBride, Faiz Anwer
We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...
February 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29388036/anaplastic-plasmacytoma-a-rare-tumor-presenting-as-a-pathological-fracture-in-a-younger-adult
#13
Robert W Morris, Varsha Kumar, Ali G Saad
Solitary plasmacytoma is the rarest type of plasma cell neoplasm, and the anaplastic form is even more uncommon. Plasmacytoma most commonly originates in bone and predominantly affects older patients. We describe the case of a 35-year-old woman with solitary osseous anaplastic plasmacytoma that presented initially with a pathological fracture following minor trauma. The patient was immunocompetent and had no predisposing conditions for a plasma cell tumor. Left lower extremity radiographs revealed an oblique fracture of the distal femur, and CT imaging indicated a primary osseous lesion at the fracture site...
January 31, 2018: Skeletal Radiology
https://www.readbyqxmd.com/read/29372735/isolation-of-circulating-plasma-cells-from-blood-of-patients-diagnosed-with-clonal-plasma-cell-disorders-using-cell-selection-microfluidics
#14
Joyce W Kamande, Maria A M Lindell, Małgorzata A Witek, Peter M Voorhees, Steven A Soper
Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0...
February 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29372057/right-orbital-edema-masquerading-a-hematologic-malignancy
#15
Andrew C Tiu, Vivian Arguello-Guerra, Gabor Varadi
Introduction: Multiple myeloma is caused by abnormal proliferation of plasma cells that affects more commonly African Americans. It classically presents with hypercalcemia, renal failure, anemia, and lytic bone lesions. The aim of this article is to present an unusual case of a 63-year-old African-American female with multiple myeloma who presented with worsening right-sided eye swelling for the past 3 weeks and to briefly review ophthalmologic manifestations of multiple myeloma. Case description: Our patient's presentation was associated with a throbbing frontal headache, nasal congestion, malaise, and weight loss...
2018: SAGE Open Medical Case Reports
https://www.readbyqxmd.com/read/29363546/myeloma-cells-are-activated-in-bone-marrow-microenvironment-by-the-cd180-md-1-complex-which-senses-lipopolysaccharide
#16
Jiro Kikuchi, Yoshiaki Kuroda, Daisuke Koyama, Naoki Osada, Tohru Izumi, Hiroshi Yasui, Takakazu Kawase, Tatsuo Ichinohe, Yusuke Furukawa
Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating the mechanisms underlying the regrowth of dormant clones may contribute to further improvement of the prognosis of MM patients. In this study, we find that the CD180/MD-1 complex, a noncanonical lipopolysaccharide (LPS) receptor, is expressed on MM cells but not on normal counterparts, and its abundance is markedly upregulated under adherent and hypoxic conditions...
April 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29333406/stat3-expression-is-associated-with-poor-survival-in-non-elderly-adult-patients-with-newly-diagnosed-multiple-myeloma
#17
Sung-Hoon Jung, Seo-Yeon Ahn, Hyun-Woo Choi, Myung-Geun Shin, Seung-Shin Lee, Deok-Hwan Yang, Jae-Sook Ahn, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Background: Signal transducer and activator of transcription 3 (STAT3) is not only a key signaling molecule in the regulation of growth but is also involved in malignant transformation. We investigated the prognostic significance of STAT3 expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly diagnosed multiple myeloma (MM). Methods: Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138...
December 2017: Blood Research
https://www.readbyqxmd.com/read/29317217/crucial-role-of-ho-1-irf4-dependent-apoptosis-induced-by-panobinostat-and-lenalidomide-in-multiple-myeloma
#18
Sishi Tang, Dan Ma, Bingqing Cheng, Qing Fang, Xingyi Kuang, Kunling Yu, Weili Wang, Bo Hu, Jishi Wang
Inhibition of histone deacetylase (HDAC) is a promising therapeutic strategy for various hematologic cancers. Panobinostat has been approved for treating patients with multiple myeloma (MM) by the FDA. Since the mechanism for the resistance of panobinostat to MM remains elusive, we aimed to clarify this mechanism and the synergism of panobinostat with lenalidomide. The mRNA and protein of transcription factor IRF4 were overexpressed in CD138+ mononuclear cells from MM patients compared with in those from healthy donors...
February 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29273733/knockdown-of-long-non-coding-rna-h19-inhibits-multiple-myeloma-cell-growth-via-nf-%C3%AE%C2%BAb-pathway
#19
Yuanyuan Sun, Jing Pan, Ning Zhang, Wei Wei, Shanshan Yu, Limei Ai
Long non-coding RNAs (lncRNAs) are implicated in the complex network of cancer including Multiple myeloma (MM) and play important roles in tumor development. lncH19 was significantly up-regulated in multiple cancer types, suggesting it is a potential oncogene. However, the exact functions and downstream mechanisms are largely unknown. This study aimed to investigate whether H19 participates in the cell growth of MM and elucidate the underlying mechanism. We found that H19 was abnormally overexpressed in MM cell lines and sorted CD138+ MM bone marrow tissues...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29205163/extramedullary-plasmacytoma-of-the-testicle
#20
Diego M Carrion, Mario Álvarez-Maestro, Juan Gómez Rivas, Pilar González-Peramato, Jesús Cisneros Ledo
OBJECTIVE: We present the case of a patient diagnosed with a testicular extramedullary plasmacytoma (EMP), and perform a brief review of the literature of this pathology. METHODS: A 64 year-old male patient, with history of multiple myeloma successfully treated three years before, presented with left testicular swelling. Initial work-up was compatible with a testicular tumor and radical inguinal orchiectomy was performed. RESULTS: Histologic examination of the testis revealed extensive intertubular infiltration by CD138 and CD56 atypical plasma cells, with diffuse staining for IgA, compatible with EMP...
December 2017: Archivos Españoles de Urología
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